Inorganic phosphate (Pi) is an important polyanion needed for ATP synthesis and bone formation. As it is found at millimolar levels in plasma, it is usually incorporated as a constituent of artificial CSF formulations for maintaining brain slices. In this paper, we show that Pi limits the extracellular zinc concentration by inducing metal precipitation. We present data suggesting that amino acids like histidine may counteract the Pi-induced zinc precipitation by the formation of soluble zinc complexes. We propose that the interplay between Pi and amino acids in the extracellular space may influence the availability of metals for cellular uptake.